Hideyuki Kawauchi

Background: The EPOS guidelines promote cellular analysis as a primary goal in endotyping chronic rhinosinusitis (CRS). Current analysis is mainly based on biopsy or operative tissue collection, whereas the use of sinonasal secretions for inflammatory endotyping is not advocated in clinical practice. Early endotyping is crucial though, especially regarding the increasing evidence of patient-tailored therapy. We aimed to investigate the diagnostic value and reproducibility of sinonasal secretions sampling. Methods: First, preoperative secretion analysis of 53 Caucasian CRS patients was compared to subsequent operative tissue analysis. Second, secretion analysis at two different time points was compared for 10 postoperative Caucasian CRS patients with type 2 (T2) inflammation and 10 control participants. Secretions were collected by both endoscopic aspiration and nasal blown secretions in all participants. Results: The sensitivity to detect T2 inflammation was higher in nasal aspiration samples (85%) compared to nasal blow secretions (32%). A specificity of 100% for both techniques was obtained. A 90% reproducibility for T2 eosinophil detection was found by sampling at different time points regardless of the technique. Of the T2 patients, 60% showed no T2 inflammatory pattern more than one year after endoscopic sinus surgery. Conclusions: Nasal secretion sampling, especially aspiration of nasal secretions, is useful in the detection of T2 inflammation in CRS pathology. We proposed a structured histopathology analysis to be useful in daily clinical practice, which includes Congo red staining sensitive for eosinophilic cells and free eosinophil granules. Analysis of nasal secretions enables endotyping in an early stage, allowing more directed therapy.

Background: Microbial infection or exposure to endotoxin later in life exacerbates established asthma. Mast cells are involved in the exacerbation of asthma. This exacerbation involves a toll-like receptor (TLR)–mediated response of mast cells. In the clinical practice of otolaryngology, otolaryngologists experience an exacerbation of nasal congestion when infectious rhinitis develops in patients with allergic rhinitis, but the mechanisms are unknown. Therefore, this study investigated the effect of lipopolysaccharide (LPS) on allergic rhinitis using a mouse allergic rhinitis model. Methods: Female BALB/c mice, TLR4 gene mutant C3H/HeJ mice or mast cell–deficient WBB6F1-^W/Wv mice were sensitized intraperitoneally with ovalbumin (OVA)/alum, and were intranasal challenged with OVA and/or LPS. Nasal symptoms and histologic changes were examined. Cytokines in nasal tissue were examined by Western blot. The effects of LPS on degranulation and cytokine production of bone marrow–derived mast cells (BMMCs) were investigated. Results: Nasal administration of LPS together with the antigen exacerbated nasal symptoms, eosinophil infiltration of the nasal mucosa, and increased IL-5 production in the nasal mucosa. It was not observed in C3H/HeJ mice and WBB6F1-^W/Wv mice. The addition of LPS increased the production of IL-5 from BMMCs in a dose-dependent manner, but no effect on degranulation was observed. Conclusions: Intranasal administration of LPS exacerbates allergic rhinitis through Th2 cytokine production from mast cells. This observation provides clues to the mechanism of exacerbation of allergic rhinitis caused by an infection in daily clinical practice.

Objective: Sublingual immunotherapy has been considered to be a painless and effective therapeutic treatment of patients with allergic rhinitis. Its mechanism of action has been elucidated, but there are still controversies among many reports between clinical efficacy and laboratory data. Therefore, its mechanism of action needs to be investigated further by using promising animal models such as rodents and monkeys. Materials and Methods: Bearing this in mind, in our present study, we successfully constructed an effective murine model for sublingual immunotherapy (SLIT) in allergic rhinitis in which mice were sublingually administered ovalbumin (OVA), followed by intraperitoneal (ip) sensitization and intranasal (i.n.) challenge of OVA. Results: To summarize our experimental data, nasal symptoms such as sneezing and nasal rubbing of sublingually treated mice were significantly attenuated in accordance with lower specific IgE antibodies in sera. Histological analysis of eosinophil recruitment in nasal mucosae reveals less allergic inflammation in sublingually treated mice. Interleukin-10 (IL-10) production and IL-10–specific mRNA gene expression of cultured submandibular lymph node (SMLN) cells with OVA, obtained from sublingually treated mice, were significantly higher than those of mice without sublingual treatment. Conclusion: These results demonstrate that sublingually introduced antigens can actually attenuate nasal symptoms in a murine allergic rhinitis model upon allergen exposures. Furthermore, our immunological data might indicate an important role of IL-10 producing T cells in SMLN to control nasal allergic reaction.

Türk Otorinolarengoloji Arşivi

Chronic rhinitis is defined as an inflammation of the nasal epithelium, and is characterized by the presence of two or more specific nasal symptoms including obstruction, rhinorrhea, sneezing, and/or itching for at least 12 weeks. In childhood, this clinical entity is very common and carries a significant socioeconomic burden. The impact on the physical, social, and psychological well-being of family cannot be underestimated. Rhinitis is an umbrella term which includes different phenotypes of rhinitis with distinct underlying pathophysiologic mechanisms. In most cases the diagnosis of rhinitis is rather straightforward; however, sometimes when based on clinical symptomatology, characterization may be challenging. Herein, we provide guidance for getting all the data needed for the differential diagnosis of rhinitis based on medical history and clinical examination.

The concept of united airway disease comprises allergic rhinitis (AR) with asthma, and eosinophilic chronic rhinosinusitis (ECRS) with asthma. It embodies a comprehensive approach to the treatment of upper and lower airway inflammation. The treatment of upper airway inflammation reduces asthma symptoms and decreases the dose of inhaled corticosteroids (ICS) necessary to treat asthma. However, little is known about the mechanisms of interaction between upper and lower airway inflammation. Here we review these mechanisms, focusing on neural modulation and introduce a novel therapeutic approach to united airway disease using a fine-particle ICS. Our understanding of the relationship between the upper and lower airways and its contribution to T helper 2 (Th2)-skewed disease, such as AR and/or ECRS with asthma, has led us to this novel therapeutic strategy for a comprehensive approach to the treatment of upper airway inflammation with asthma.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory upper airway disease, accompanied mainly by eosinophilia and/or asthma. In addition, the disease correlates with a high rate of hyposmia, following a marked infiltration of eosinophils into the inflamed site, the paranasal sinus. Although eosinophils are known to contribute to the development of hyposmia and CRSwNP pathology, the underlying mechanisms remain unclear. This study aimed to investigate whether eosinophilic upper airway inflammation induces hyposmia and CRSwNP in a murine model using an adoptive transfer system. Methods: To induce eosinophilic rhinosinusitis, splenocytes, including a high proportion (over 50%) of activated eosinophils (SPLhEos), were collected from interleukin-5 transgenic mice following double intraperitoneal injections of antigens, such as ovalbumin, house dust mite, or fungus. Activated SPLhEos with corresponding antigens were then transferred into the nasal cavity of recipient mice, which were sensitized and challenged by the corresponding antigen four times per week. Olfactory function, histopathological, and computed tomography (CT) analyses were performed 2 days after the final transfer of eosinophils. Results: Hyposmia was induced significantly in mice that received SPLhEos transfer compared with healthy and allergic mice, but it did not promote morphological alteration of the paranasal sinus. Pathological analysis revealed that epithelial layer injury and metaplasia similar to polyps, with prominent eosinophil infiltration, was induced in recipient tissue. However, there was no nasal polyp development with interstitial edema that was similar to those recognized in human chronic rhinosinusitis. Conclusions: This study supports the previously unsuspected contribution of eosinophils to CRS development in the murine model and suggests that murine-activated eosinophilic splenocytes contribute to the development of hyposmia due to more mucosal inflammation than physical airway obstruction and epithelial layer injury with convex lesions.